| Project/Area Number |
12470511
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Environmental pharmacy
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| Research Institution | Tokyo University of Science |
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Principal Investigator |
TAKEDA Ken Tokyo University of Science, Faculty of Pharmaceutical Science, Professor, 薬学部, 教授 (80054013)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥14,000,000 (Direct Cost: ¥14,000,000)
Fiscal Year 2002: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2001: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥7,600,000 (Direct Cost: ¥7,600,000)
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| Keywords | diesel exhaust / maternal exposure / Mullerian inhibiting substance (MIS) / steroidgenic factor-1(Ad4BP / SF-1 / testosteron / male reproductive system / daily sperm production / male accessory gland / 胎仔期暴露 / ミュラー管阻害因子(MIS) / テストステロンの血中濃度 / 内分泌かく乱 / 生殖系 / 生殖腺分化 / SF-1 / MIS / エストロゲンレセプター / Steroidgenic factor-1 / Mullerian Inhibitory Substance |
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| Research Abstract |
We investigated the effect of exposure of pregnant mice to diesel exhaust on male gonad development at the level of mRNA expression. Expression of mRNAs for steroidogenic factor-1 (Ad4BP/SF-1) and Mullerian inhibitory substance (MIS), which are essential for male gonadal differentiation, decreased significantly in male fetuses when maternal mice were exposed to diesel exhaust at levels of 0.1 mg and 3.0 mg diesel exhaust particles (DEP)/m^3 for 8 hours per day between days 2 and 13 post coitum. Expression levels of mRNAs for steroidogenic cytochrome P450 genes regulated by Ad4BP/SF-1, especially 3β-hydroxysteroid dehydrogenase (3β-HSD) and aromatase, were also decreased by exposure to diesel exhaust. There were no significant differences in levels of estrogen receptor (ER) and androgen receptor (AR) mRNAs between control and exposed mice. The data indicate that exposure of pregnant mice to diesel exhaust affects the expression of genes essential in the early stages of embryonic development.
The effects of in utero exposure to diesel exhaust (DE) on the mouse malereproductive system after birth was examined. Various markers that appear in pups were assessed. Pregnant ICR mice inhaled DE at DEP concentrations of 0.3,1.0,or 3.0 mg DEP/m3 or clean air, as the control, on days 2-16 days post coitum. On postnatal day (PND) 28, the weight of the testes and accessory glands, and testosterone concentration in serum were significantly higher in the DE-exposed male pups. Testosterone concentration correlated significantly (P<0.01) with the expression of steroidogenic enzyme mRNAs, weight of the testes and male reproductive accessory glands, and daily sperm production. These findings indicate that very early stage mouse embryo exposure to DE leads to endocrine disruption after birth.
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